Kazuko Kawamura

Serum C-reactive protein levels can be used to predict future ischemic stroke and mortality in Japanese men from the general population

BACKGROUND High C-reactive protein (CRP) levels have been reported to be associated with an increased risk of atherosclerotic cardiovascular events. The relationship of CRP levels to the risk of cerebrovascular events in the Japanese population, which has a lower prevalence of coronary artery disease and a lower CRP level than Western populations, has not been fully clarified. The present study examined the predictive value of serum high sensitivity CRP (hs-CRP) levels for future cerebrovascular events and mortality in the general Japanese population. METHODS The subjects for this community-based, prospective cohort study were recruited from the general population (n=7901, male only, mean age=64.0 years). Serum hs-CRP levels and cardiovascular risk factors were determined at baseline. The mean follow-up period was 2.7 years. After excluding subjects with a cardiovascular history, the relationships between hs-CRP levels and cerebrovascular events and mortality were assessed. RESULTS During follow-up, 130 participants had a first stroke (95 ischemic strokes), and 161 participants died. The hs-CRP tertile level was a significant predictor for a first ischemic stroke (3rd tertile, HR=1.77: 95% Cl, 1.04-3.03, compared with the 1st tertile), after adjustment for age and classical cardiovascular risk factors. Similar trends were observed for the prediction of all-cause mortality (3rd tertile, HR=2.26: 95% Cl, 1.49-3.42, compared with the 1st tertile). CONCLUSION CRP levels can be used to predict future ischemic stroke and mortality in Japanese men from the general population, independently from traditional cardiovascular risk factors.

Predictive value of plasma B-type natriuretic peptide for ischemic stroke: a community-based longitudinal study.

OBJECTIVE Structural heart diseases including atrial fibrillation are precursors for ischemic stroke. Plasma B-type natriuretic peptide (BNP) has been reported to be increased in patients with several types of structural heart diseases. However, the predictive value of plasma BNP for ischemic stroke remains unknown. We have studied the predictive ability of plasma BNP for future development of stroke in community dwelling adults. METHODS Subjects of this community-based study were recruited from the general population (n=13,466). Plasma BNP levels and cardiovascular risk factors were determined at baseline. The incidence of ischemic stroke in the cohort was identified from regional stroke registry data. A multivariate Cox regression analysis was performed to analyze the relationship between plasma BNP levels and the risk of stroke. RESULTS During a mean follow-up period of 2.8 years, 102 participants (65 males, 37 females) experienced a first ischemic stroke. In men, after adjustment for classical cardiovascular risk factors and atrial fibrillation, the hazard ratio (HR) for ischemic stroke was significantly elevated in the highest plasma BNP quartile (HR=2.38; 95% CI=1.07-5.29). In women, the relationship between plasma BNP levels and risk of ischemic stroke was of marginal significance after adjusting for the presence or absence of atrial fibrillation (HR=3.03; 95% CI=0.84-10.92, P=0.09). CONCLUSION Elevated plasma BNP levels predict the risk of ischemic stroke within men from the general population.

Cardiovascular risk factors in the Japanese northeastern rural population

BACKGROUND People living in the northeastern part of Japan have high prevalences of hypertension and stroke. The current status of cardiovascular risk factors in them should be elucidated. METHODS The survey was carried out from 2002 to 2004 in the northeastern part of the main island of Japan. A total of 26,472 Japanese men and women were enrolled (acceptance rate: 84.5%). Sex- and age-specific prevalences of cardiovascular risk factors were determined. Mean values of predictive markers (high-sensitivity C reactive protein (hsCRP), brain natriuretic peptide (BNP) and microalbuminuria) were also determined in each group. Risk factor-related variables in non-hypertensive subjects and hypertensive subjects were compared. RESULTS Proportions of subjects with hypertension, diabetes and dyslipidemia were 46.0%, 7.6%, and 30.3%, respectively, in males and 38.6%, 4.0%, and 38.5%, respectively, in females. Mean values of hsCRP and BNP were 1.41 mg/L and 26.5 pg/mL, respectively, in males and 1.01 mg/L and 23.7 pg/mL, respectively, in females. Proportions of male and female subjects with microalbuminuria were 22.0% and 23.4%, respectively. These markers become higher with advance of age. Prevalence of atrial fibrillation was 1.56%, and it increased with advance of age in both men and women. High prevalences of cardiovascular risk factors in this area were found. Hypertensive subjects who did not take anti-hypertension medication accounted for about 20% of total subjects and their blood pressure remained poorly controlled. CONCLUSION Attention should be given to cardiovascular risk factors in the Japanese northeastern rural population.

Comparison of low-density lipoprotein cholesterol concentrations measured by a direct homogeneous assay and by the Friedewald formula in a large community population

BACKGROUND We compare the direct homogeneous low-density lipoprotein cholesterol (LDL-C) assay with the Friedewald formula (FF) for determination of LDL-C in a large community-dwelling population. METHODS A total of 21,194 apparently healthy subjects aged 40 to 79 years with triglyceride (TG) concentrations <4.52 mmol/l were enrolled. LDL-C were directly measured by the enzymatic homogeneous assay (LDL-C (D)) and also estimated by the FF (LDL-C (F)). Paired t-test, Pearsons correlation coefficient and linear regression analysis were performed and the concordances of the National Cholesterol Education Program (NCEP) risk category were estimated. RESULTS Both in fasting (n=3270) and nonfasting samples (n=17,924), LDL-C (D) highly correlated with LDL-C (F): r=0.971 and 0.955, respectively. Concordant results for NCEP categories were 84.8% for fasting samples and 80.1% for nonfasting samples. However, the bias between the 2 measurements increased in samples with TG concentrations >1.69 mmol/l, especially in nonfasting samples. CONCLUSIONS The results showing less variability of the direct LDL-C assay than that of the FF in nonfasting samples suggest that epidemiological studies can use LDL-C measured by the direct assay both in fasting and nonfasting samples.

Dietary intake of n-3 polyunsaturated fatty acids is inversely associated with CRP levels, especially among male smokers

OBJECTIVE To examine whether dietary intake of n-3 polyunsaturated fatty acid (n-3PUFA) is associated with serum C-reactive protein (CRP) levels with regard to smoking status in the Japanese general population in a cross-sectional study. METHODS AND RESULTS A total of 14,191 participants aged 40-69 years were enrolled and divided into quartile groups according to their intake of n-3PUFA. Multivariate-adjusted logarithm-transformed CRP levels were compared between the quartile groups with regard to smoking status after adjusting for traditional risk factors and intake of saturated fatty acids. Adjusted CRP levels were inversely associated with dietary intake of n-3PUFA for both the male subjects and female subjects (p<0.05 for trend). A linear trend was not seen between intake of n-3PUFA and adjusted CRP levels in male nonsmokers. Adjusted CRP level in the lowest quartile group of n-3PUFA was significantly higher than the levels in other groups in male smokers. CONCLUSION Sufficient dietary intake of n-3PUFA may attenuate inflammatory reaction and this effect is more evident among high-risk populations such as male smokers although the small numbers of female ex-smokers and nonsmokers limited statistical power to draw strong conclusions about these groups.

Standardized Prevalence Ratios for Chronic Hepatitis C Virus Infection Among Adult Japanese Hemodialysis Patients

Background Many studies have estimated the prevalence of anti-hepatitis C virus (HCV) antibody among hemodialysis (HD) patients; however, the prevalence of HCV core antigen—which indicates the presence of chronic HCV infection—is not known. Methods Standardized prevalence ratios (SPRs) for anti-HCV antibody and HCV core antigen among HD patients (n = 1214) were calculated on the basis of data from the general population (n = 22 472) living in the same area. Results The prevalences of anti-HCV antibody and HCV core antigen were 12.5% and 7.8%, respectively, in male hemodialysis patients, and 8.5% and 4.1% in female hemodialysis patients. The SPRs (95% confidence interval) for anti-HCV antibody and HCV core antigen were 8.39 (6.72–10.1) and 12.9 (9.66–16.1), respectively, in males, and 5.42 (3.67–7.17) and 8.77 (4.72–12.8) in females. Conclusions The prevalences of chronic HCV infection among male and female HD patients were 13-fold and 9-fold, respectively, those of the population-based controls. Further studies should therefore be conducted to determine the extent of chronic HCV infection among HD patients in other populations and to determine whether chronic HCV infection contributes to increased mortality in HD patients.

Seropositivity for Anti-HCV Core Antigen is Independently Associated With Increased All-Cause, Cardiovascular, and Liver Disease-Related Mortality in Hemodialysis Patients

Background It is not known whether chronic or past hepatitis C virus (HCV) infection contributes to the high mortality rate in hemodialysis patients. Methods This prospective study of 1077 adult hemodialysis patients without hepatitis B virus infection used Poisson regression analysis to estimate crude and sex- and age-adjusted rates (per 1000 patient-years) of all-cause, cardiovascular, infectious disease-related and liver disease-related mortality in patients negative for HCV antibody (group A), patients positive for HCV antibody and negative for anti-HCV core antigen (group B), and patients positive for anti-HCV core antigen (group C). The relative risks (RRs) for each cause of death in group B vs group C as compared with those in group A were also estimated by Poisson regression analysis after multivariate adjustment. Results A total of 407 patients died during the 5-year observation period. The sex- and age-adjusted mortality rate was 71.9 in group A, 80.4 in group B, and 156 in group C. The RRs (95% CI) for death in group B vs group C were 1.23 (0.72 to 2.12) vs 1.60 (1.13 to 2.28) for all-cause death, 0.75 (0.28 to 2.02) vs 1.64 (0.98 to 2.73) for cardiovascular death, 1.64 (0.65 to 4.15) vs 1.58 (0.81 to 3.07) for infectious disease-related death, and 15.3 (1.26 to 186) vs 28.8 (3.75 to 221) for liver disease-related death, respectively. Conclusions Anti-HCV core antigen seropositivity independently contributes to elevated risks of all-cause and cause-specific death. Chronic HCV infection, but not past HCV infection, is a risk for death among hemodialysis patients.

Gender-specific risk stratification with plasma B-type natriuretic peptide for future onset of congestive heart failure and mortality in the Japanese general population.

BACKGROUND Elevated plasma B-type natriuretic peptide (BNP) levels suggest a high risk for future onset of cardiovascular events including congestive heart failure (CHF) and mortality. In the general population, although median plasma BNP levels have been reported to be higher in women than in men, the incidence of CHF and mortality are lower in women. However, no studies have examined gender-specific risk stratification of plasma BNP levels for future onset of CHF and mortality. METHODS Subjects of this study were recruited from our general population. Baseline data including plasma BNP were determined in 13,466 subjects (men 4527, women 8939; median age = 64 yrs). A multivariate Cox regression analysis was performed to examine the predictive ability of plasma BNP for new onset of CHF and mortality. RESULTS The mean follow-up duration was 2.9 years. After adjustment for traditional cardiovascular risk factors including atrial fibrillation, hazard ratios for CHF development for values above the 75th percentile of BNP were 13.4 (p<0.001) in men and 8.5 (p<0.001) in women. Similarly, each increment of 1SD in log BNP levels increased the hazard ratio by 8.8 (p<0.001) in men, and 6.7 (p<0.001) in women. The area under the receiver operating characteristic curve was significant for prediction of the onset of CHF (men; 0.853, women; 0.838). In addition, increased plasma BNP levels implied high risk of any-cause mortality in men (above the 75th percentile; hazard ratio = 1.8, p=0.005: increment of 1SD; hazard ratio = 1.4, p=0.024), but this relationship was suboptimal in women. CONCLUSION Measurements of plasma BNP provides strong predictive information about future onset of CHF in both sexes, with predictive ability for death being effective especially in men.

Serum polyunsaturated fatty acid composition and serum high-sensitivity C-reactive protein levels in healthy Japanese residents: The KOBE study

Background/ObjectivesSerum polyunsaturated fatty acid (PUFA) composition reflects dietary intake and is related to risks for cardiovascular diseases. We hypothesized that serum n-3 PUFA composition, especially including long-chain n-3 PUFA such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is associated with inflammatory status, which is related to increased risk for cardiovascular diseases.Subjects/MethodsWe investigated the relationship between serum PUFA composition and high-sensitivity C-reactive protein (hs-CRP) levels in a cross-sectional study among 1,102 healthy men and women aged 40–74 years who reside in Kobe City. Multiple linear regression models that predict hs-CRP level were prepared to confirm the contribution of serum total n-3 PUFA, long-chain n-3 PUFA, EPA and DHA compositions after adjusting for other PUFAs and atherosclerotic risk factors.ResultsThe serum n-3 PUFA, particularly long-chain n-3 PUFA, compositions were inversely associated with the hs-CRP levels. The standardized regression coefficient was −0.089 (p < 0.01) for total n-3 PUFA, −0.091 (p < 0.01) for long-chain n-3 PUFA, −0.071 (p = 0.03) for EPA, and −0.068 (p = 0.04) for DHA. The n-6 PUFA compositions were also inversely associated with the hs-CRP levels (−0.169 [p < 0.01] for total n-6 PUFA and −0.159 [p < 0.01] for linoleic acid).ConclusionsThe serum n-3 PUFA compositions were inversely related with the hs-CRP levels, similar associations were also observed in n-6 PUFA compositions. Our results suggest that dietary PUFA intake was inversely associated with attenuated inflammation in healthy Japanese population.